Majoor-Krakauer D, Ottman R, Johnson W G, Rowland L P
G.H. Sergievsky Center, Columbia University, New York, NY 10032.
Neurology. 1994 Oct;44(10):1872-7. doi: 10.1212/wnl.44.10.1872.
Clinicians have long suspected an association of classic amyotrophic lateral sclerosis (ALS) with Parkinson's disease (PD), dementia, or both. If proven, this would raise the possibility of a shared genetic susceptibility to the three disorders. To investigate this hypothesis, we compared 151 newly diagnosed ALS patients (seven familial) with 140 controls in terms of cumulative incidence of ALS, PD, and dementia in parents, siblings, and grandparents. We used Cox proportional hazards analysis to compute rate ratios (RRs) for ALS, dementia, and PD in relatives of ALS patients versus relatives of controls. The risk for dementia was significantly higher in relatives of ALS patients than in those of controls (RR = 1.9; 95% CI 1.1-3.1) and was similar for relatives of patients with sporadic and familial ALS. The risk of PD was higher in relatives of patients with familial ALS (RR = 5.6; 95% CI 0.6-50.3) than in relatives of patients with sporadic ALS (RR = 1.8; 95% CI 0.5-6.0), but these differences were not statistically significant, probably due to insufficient statistical power with the available sample size. These findings indicate that ALS and dementia, and perhaps also PD, co-occur within families more often than expected by chance, suggesting that there may be a shared genetic susceptibility to these disorders.
长期以来，临床医生一直怀疑经典型肌萎缩侧索硬化症（ALS）与帕金森病（PD）、痴呆症或两者之间存在关联。如果得到证实，这将增加这三种疾病存在共同遗传易感性的可能性。为了研究这一假设，我们比较了151名新诊断的ALS患者（7例家族性患者）和140名对照者的父母、兄弟姐妹及祖父母中ALS、PD和痴呆症的累积发病率。我们使用Cox比例风险分析来计算ALS患者亲属与对照者亲属患ALS、痴呆症和PD的比率（RR）。ALS患者亲属患痴呆症的风险显著高于对照者亲属（RR = 1.9；95%置信区间1.1 - 3.1），散发性和家族性ALS患者的亲属情况相似。家族性ALS患者亲属患PD的风险高于散发性ALS患者亲属（RR = 5.6；95%置信区间0.6 - 50.3），而散发性ALS患者亲属的RR为1.8（95%置信区间0.5 - 6.0），但这些差异无统计学意义，可能是由于现有样本量的统计效力不足。这些发现表明，ALS和痴呆症，或许还有PD，在家族中同时出现的频率高于偶然预期，提示这些疾病可能存在共同的遗传易感性。
